Atherosclerosis remains a major cause of mortality in the US. Even a more striking statistic is subjects with Type 2 diabetes are 4 to 5 times more likely to suffer a heart attack than someone without diabetes. Although much has been learned about the vascular cell components that contribute to atherosclerosis, it has only recently become accepted that immune cells play an important role in atherosclerosis. The mechanisms for how immune cells modulate atherosclerosis are unclear, and this is an emerging field of research that could lead to promising new therapies. We are a long-standing team of investigators who have been studying atherosclerosis and type 2 diabetes for the last 15 years. The focus of this PPG renewal is to study the immunobiology of atherosclerosis. Project 1 will study T regulatory lymphocyte function in atherosclerosis. Project 2 will investigate the synergy between endotoxemia and oxidized cholesteryl esters in TLR-mediated vascular inflammation. Project 3 will test the role of the transcriptional repressor ld3 in modulating B lymphocyte function in atherosclerosis. A Human Phenotyping and Immune Cell Core will provide human blood samples for immune cell phenotyping for each project. The purpose of this Administrative Core (Core A) is to coordinate the PPG by providing scientific administration, grant and fiscal management, and coordination of scientific advisory meetings.